RARE Daily

FDA Grants Fast Track Status to Regenxbio DMD Gene Therapy and Kala’s Ocular Cell Therapy Candidates

April 12, 2023

Rare Daily Staff

The U.S. Food and Drug Administration granted Fast Track designation to two companies, Regenxbio and Kala Pharmaceuticals, developing treatments for rare diseases.

Fast Track designation aims to facilitate the development and expedite the review of new therapeutics that are intended to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs. Therapies granted this designation are given the opportunity for more frequent interactions with the FDA and may qualify for priority review.

The FDA granted Fast Track designation for Regenxbio’s RGX-202, a potential one-time gene therapy for the treatment of Duchenne muscular dystrophy, a rare genetic disorder, caused by mutations in the gene responsible for making dystrophin, a protein important for muscle cell structure and function. The absence of functional dystrophin protein results in cell damage during muscle contraction, leading to cell death, inflammation, and fibrosis in muscle tissues. Over time, individuals with Duchenne experience progressive muscle weakness and eventually lose the ability to walk. Respiratory and heart muscles are also affected, leading to difficulty breathing, cardiomyopathy, and death. There is presently no cure for Duchenne.

“Fast Track designation, along with our capabilities to conduct our clinical trials using commercial-scale cGMP material, will further support the efficient development of RGX-202 from clinic to commercial readiness,” said Kenneth Mills, president, and CEO of Regenxbio. “We look forward to reporting initial data from our clinical trial of RGX-202 in the second half of this year.”

RGX-202 is designed to deliver a transgene for a novel micro dystrophin that includes the functional elements of the C-Terminal (CT) domain found in naturally occurring dystrophin. The presence of the CT domain has been shown in preclinical studies to recruit several key proteins to the muscle cell membrane, leading to improved muscle resistance to contraction-induced muscle damage in dystrophic mice. RGX-202 is designed to support the delivery and targeted expression of genes throughout skeletal and heart muscle using the NAV AAV8 vector, a vector used in numerous clinical trials, and a well-characterized muscle-specific promoter. RGX-202 has been granted Fast Track, Orphan Drug and Rare Pediatric Disease designations by the FDA.

In January, Regenxbio began actively recruiting patients in the phase 1/2 AFFINITY DUCHENNE trial, a multicenter, open-label dose evaluation and dose expansion clinical study to evaluate the safety, tolerability, and clinical efficacy of a one-time intravenous (IV) dose of RGX-202 in patients with Duchenne. Six ambulatory, pediatric patients (ages 4 to 11 years old) with Duchenne are expected to enroll in two cohorts of different doses. After an independent safety data review for each cohort, a dose expansion phase of the trial may allow for up to six additional patients to be enrolled at each dose level (for a total of up to nine patients in each dose cohort).

Additionally, Regenxbio is recruiting patients in the AFFINITY BEYOND trial, an observational screening study to evaluate the prevalence of AAV8 antibodies in patients with Duchenne up to 12 years of age. Information collected in this study may be used to identify potential participants for the AFFINITY DUCHENNE trial and potential future trials of RGX-202.

The FDA also granted Fast Track designation for Kala Pharmaceuticals’ human mesenchymal stem cell secretome (MSC-S) therapy (KPI-012) for the treatment of persistent corneal epithelial defect (PCED), a rare and debilitating ocular condition.

Persistent corneal epithelial defect, which is defined as a persistent non-healing corneal defect or wound that is refractory to conventional treatments, is a rare disease with an estimated incidence in the United States of 100,000 cases per year and 238,000 cases per year in the United States, European Union and Japan combined. PCED can have various etiologies, including neurotrophic keratitis, surgical epithelial debridement, microbial/viral keratitis, corneal transplant, limbal stem cell deficiency and mechanical and chemical trauma and, if left untreated, can lead to infection, corneal ulceration or perforation, scarring, opacification, and significant vision loss.

Based on a multifactorial mechanism of action and preclinical and clinical data generated to-date, Kala believes KPI-012 may represent a significant advancement in the treatment of PCED and could become the first approved treatment for PCED across all its various etiologies.

“There is a significant unmet need for patients suffering from PCED, which can lead to many complications and sequelae, including vision impairment, infection, corneal perforation and significant pain and discomfort. There are currently no approved pharmaceutical treatments for the majority of PCED patients, and KPI-012’s multifactorial mechanism of action is a potential solution to address all underlying etiologies of PCED,” said Kim Brazzell, head of R&D and chief medical officer at Kala Pharmaceuticals.

In February 2023, Kala dosed the first patient in its CHASE (Corneal Healing After SEcretome therapy) phase 2b trial evaluating KPI-012 for the treatment of PCED. In March 2023, Kala reported positive safety data from the first cohort of two patients that were treated with a high dose of KPI-012 four times per day. Both patients successfully completed at least one week of dosing with no safety issues observed and the trial has now advanced to Cohort 2. The second cohort is a multicenter, randomized, double-masked, vehicle-controlled, parallel-group study to evaluate the safety and tolerability of two doses of KPI-012 in ophthalmic solution versus vehicle dosed topically QID for 56 days in approximately 90 patients. The primary endpoint of the trial is the complete healing of the PCED as measured by corneal fluorescein staining. Kala is targeting reporting topline safety and efficacy data in the first quarter of 2024. If the results are positive, and subject to discussion with regulatory authorities, Kala believes this trial could serve as the first of two pivotal trials required to support the submission of a Biologics License Application to the FDA.

KPI-012 has received Orphan Drug and Fast Track designations from the FDA.

Photo: Kenneth Mills, president, and CEO of Regenxbio

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